Evidence map›Paper›PMID 37554444›Full record

ArticleiScience2023

The SWI/SNF complex member SMARCB1 supports lineage fidelity in kidney cancer.

Ludovic Wesolowski, Jianfeng Ge, Leticia Castillon, Debora Sesia, Anna Dyas, Shoko Hirosue, Veronica Caraffini, Anne Y Warren, Paulo Rodrigues, Giovanni Ciriello and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in iScience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.8field-weighted citation impact, top 27% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 3 countries.

Ludovic WesolowskiMRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge Biomedical Campus, Box 197, Cambridge CB2 0XZ, UK.
Jianfeng GeMRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge Biomedical Campus, Box 197, Cambridge CB2 0XZ, UK.
Leticia CastillonTranslational Cancer Medicine Program, Faculty of Medicine, Biomedicum Helsinki, University of Helsinki, 00014 Helsinki, Finland.
Debora SesiaDepartment of Computational Biology, University of Lausanne (UNIL), 1015 Lausanne, Switzerland.
Anna DyasMRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge Biomedical Campus, Box 197, Cambridge CB2 0XZ, UK.
Shoko HirosueMRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge Biomedical Campus, Box 197, Cambridge CB2 0XZ, UK.
Veronica CaraffiniMRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge Biomedical Campus, Box 197, Cambridge CB2 0XZ, UK.
Anne Y WarrenDepartment of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK.
Paulo RodriguesMRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge Biomedical Campus, Box 197, Cambridge CB2 0XZ, UK.
Giovanni CirielloDepartment of Computational Biology, University of Lausanne (UNIL), 1015 Lausanne, Switzerland.
Saroor A PatelMRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge Biomedical Campus, Box 197, Cambridge CB2 0XZ, UK.
Sakari VanharantaMRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge Biomedical Campus, Box 197, Cambridge CB2 0XZ, UK.
University of Cambridge · GBSwiss Cancer Center Léman · CHUniversity of Helsinki · FICambridge University Hospitals NHS Foundation Trust · GB

Funding

Medical Research Council MC_UU_12022/7
6 · The paper itself

Abstract

Lineage switching can induce therapy resistance in cancer. Yet, how lineage fidelity is maintained and how it can be lost remain poorly understood. Here, we have used CRISPR-Cas9-based genetic screening to demonstrate that loss of SMARCB1, a member of the SWI/SNF chromatin remodeling complex, can confer an advantage to clear cell renal cell carcinoma (ccRCC) cells upon inhibition of the renal lineage factor PAX8. Lineage factor inhibition-resistant ccRCC cells formed tumors with morphological features, but not molecular markers, of neuroendocrine differentiation. SMARCB1 inactivation led to large-scale loss of kidney-specific epigenetic programs and restoration of proliferative capacity through the adoption of new dependencies on factors that represent rare essential genes across different cancers. We further developed an analytical approach to systematically characterize lineage fidelity using large-scale CRISPR-Cas9 data. An understanding of the rules that govern lineage switching could aid the development of more durable lineage factor-targeted and other cancer therapies.

Indexed as

CancerCellular physiologyHuman geneticsMedical microbiology

Identifiers

PMID37554444
PMCPMC10405256
OpenAlexW4384133515

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.